Field of the Disclosure
The present disclosure relates to an improved process for the preparation of fluticasone propionate.
Description of the Related Art
Fluticasone propionate is a corticosteroid of the androstane family which has potent anti-inflammatory activities and is widely accepted as a useful therapy for the treatment of inflammatory and allergic conditions such as asthma and chronic obstructive pulmonary disease (COPD).
Fluticasone propionate is chemically named as 6α, 9α-difluoro-17α-(((fluoromethyl) sulfanyl) carbonyl)-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl propionate and is represented by the following chemical structure:

U.S. Pat. No. 4,335,121 discloses a process for the preparation of fluticasone propionate, wherein 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carboxylic acid of formula IV is treated with dimethylthiocarbamoyl chloride to yield 17β-(N,N(dimethylcarbamoyl)thio)carbonyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propiony-loxy-3-oxoandrosta-1,4-diene of formula III. This is hydrolyzed by refluxing in diethyl amine to obtain the thioic acid of formula II. The compound of formula II is then reacted with bromochloromethane in the presence of sodium bicarbonate to give a chloromethylester of formula IIa. The compound of formula IIa is converted to an iodomethylester by halogen exchange, and subsequently treated with silver fluoride to yield the fluticasone propionate of formula I. The reaction steps are illustrated by the following scheme:
